The traditional visualisation of the coagulation cascade (originally published in the 1960s)1 indicates that the processes of physiological hemostasis and pathological thrombosis are tightly linked.
But a new model of the coagulation cascade suggests they are more independent than previously realized, despite their intersection at the ‘common pathway’.
Conventional anticoagulants, including direct oral anticoagulants (DOACs), all target factors within the common pathway, so unsurprisingly, they all carry a clinically significant risk of bleeding.
However, prompted by insights from genetic, epidemiologic and animal model studies, Factor XI has now emerged as a new antithrombotic target that appears non-essential for hemostasis. Targeting Factor XI may present an opportunity to pharmacologically ‘uncouple’ the two pathways, effectively suppressing the thrombosis pathway, while leaving the hemostasis pathway largely unaffected.
Through transformative hemostasis-sparing anticoagulation, the novel approach of Factor XI inhibition could potentially fulfil the ultimate ambition…
…of vital protection from thromboembolic events…
…while reducing the hazard of a clinically significant bleeding risk…
…giving physicians the confidence to prescribe to many more people…
…and a meaningful reduction in the human and socioeconomic burden of thrombotic disease
What the Experts Say
“Traditionally, thrombosis has been rather simplistically viewed as the consequence of ‘excess hemostasis’ or ‘hemostasis in the wrong place’. But recent research insights have revealed clear mechanistic differences in the pathways of pathological thrombosis and physiological hemostasis, opening up new opportunities for intervention”
Pr David Gailani : Professor of Pathology and Medicine at Vanderbilt University Medical Center, Nashville, TN, USA
“Looking beyond conventional anticoagulant targets – which are all located at the downstream intersection of these two pathways – could herald the exciting possibility of anticoagulant therapies with minimal bleeding risk….”
Pr Jeff Weitz: Professor of Medicine and Biochemistry and Biomedical Sciences at McMaster University, Hamilton, ON, Canada
Factor XI Inhibition to Uncouple Thrombosis From Hemostasis – JACC 2021
In a recent publication published in 20212, the authors provide a visual representation of the coagulation pathways that distinguishes between the steps involved in thrombosis and hemostasis to explain why factor XI inhibitors may serve as hemostasis-sparing anticoagulants. A safer class of anticoagulants would provide opportunities for treatment of a wider range of patients, including those at high risk for bleeding.Read more
Watch: Find out what experts in the field think
1 Davie EW, Ratnoff SI. Waterfall sequence for intrinsic blood clotting. Science 1964; 145: 1310–12.
2 Hsu, C. et al. J Am Coll Cardiol 2021;78(6):625–631.